This exploratory, stage 3 R21 proposal is designed to provide data on the acute treatment response of an understudied mental health population --bipolar II disorder (BDII). This disorder is characterized by major depression and periods of hypomania observable by others. There is now clear recognition of the stability of this diagnosis, and increased recognition of the severity and frequency of depressive symptoms. The overall severity, disability, and suicide risk is considered equal to bipolar I disorder. The available literature on treatment of BDII is reviewed. There are virtually no controlled acute treatment trials to direct treatment recommendations, nor is the treatment of BDII addressed in recent treatment guidelines. The most extensive data support lithium (Li) as one treatment group. Striking new findings with lamotrigine (LTG) support its efficacy in BDI acute depression and prophylaxis of rapid cycling BDII. Based on research done, including estimation of safety and tolerability, we chose to evaluate LTG and Li in this pilot study. We propose a randomized, open 16-week clinical trial comparing monotherapy Li versus LTG for sixty acutely depressed BDII patients. A physician and a blinded symptom rater will see patients every two weeks for a total of sixteen weeks. Safeguards are described to maintain patient safety. The primary aim will be to compare the relative treatment effectiveness of LTG versus Li. We hypothesize LTG will be more effective than Li at decreasing depressive symptoms. Secondary aims include assessment of tolerability, the potential of LTG to cause switching into hypomania, quality of life, and patient satisfaction. Measures will include the Hamilton Rating Scale for Depression, Montgomery-Asberg Rating Scale for Depression, Young Mania Rating Scale, Clinical Global Assessment for Bipolar Disorder, and other measures of quality of life, functioning, and physical symptoms and side effects. While full-scale intervention trials are clearly warranted in this population to establish databased recommendations for treatment, it is critical to collect pilot data to properly power and inform the design of a larger trial. This pilot study will provide data addressing the aims and sample size needed for a full-scale intervention trial.